Keri A. Baacke
Rodney K. Edwards
The care of a pregnant woman poses a special set of challenges. These challenges are due primarily to the fact that one really is caring for two separate patients: the woman and her fetus. To further complicate matters, one of these patients, the fetus, cannot be assessed directly. The needs of one often are congruent with the needs of the other. However, this may not always be the case. There are times when interventions undertaken on behalf of either the pregnant woman or her fetus may be detrimental to the other. At all times, the needs of each of these patients must be considered when caring for a pregnant woman.
Immediate Concerns
Immediate issues that need to be evaluated when caring for a pregnant woman include viability of the fetus, the gestational age of the fetus, and assessment of the fetal condition. Determination of fetal viability is the first priority in the initial assessment of a pregnant patient—a diagnosis of fetal demise eliminates the fetus as a confounding factor in decisions regarding maternal treatment. In contrast, confirmation of a live fetus indicates a need to avoid teratogenic agents and optimize oxygen delivery to the placenta. In either case, one should consider the physiologic changes that occur during pregnancy when formulating a plan of care.
Estimation of gestational age is an important factor to establish as early into the treatment as is possible. If the pregnancy is near term and nonobstetric surgical treatment is indicated, delivery of the fetus prior to such treatment may be warranted. The earliest gestational age at which neonatal survival may occur is around 23 weeks. However, survival, particularly without significant morbidity, becomes more likely at later gestational ages. Even prior to the time when ex utero survival is possible, some treatments may better be avoided for the sake of the fetus, but as the gestational age advances, discussion regarding delivery of the fetus may be appropriate to maximize treatment to the woman without placing the fetus at unnecessary risk.
Finally, fetal assessment is dependent on the current gestational age. At early gestational ages, assessment includes only documentation of fetal cardiac activity. At later gestational ages, the goal of fetal assessment and monitoring is the determination of the adequacy of fetal oxygenation, and, when necessary, alerting the physician to potential hypoxia and/or fetal compromise. These indirect assessments of the fetal condition (discussed later in this chapter) allow for intervention, with the aim of improving fetal oxygenation or delivery if improvement does not occur.
Special Considerations
When instituting therapies for a pregnant patient, the effect of such therapy on the fetus must be considered. Many treatments provided to pregnant women are also considered to be in the best interest of the fetus. Optimal maternal oxygenation, blood pressure, temperature, and electrolyte balance benefit both the mother and the fetus. Some therapies, however, may be detrimental to the fetus, such as certain radiologic procedures and the administration of some medications. Similar to the blood–brain barrier, not all medications are transported across the placenta. This fact allows the use of some treatments without undue risk to the fetus. However, there are instances when short-term use of some medications may be acceptable or when alternate therapies may provide similar benefit without excessive risk to the fetus. Certainly, all of these factors need to be considered before beginning a course of treatment. Consultation with a maternal-fetal medicine specialist will provide appropriate recommendations regarding the effects of the physiologic changes of pregnancy on the planned treatment and which medications to avoid.
Fetal Oxygenation
The placenta develops from trophoblastic cells called the syncytiotrophoblast. As these cells proliferate, the intervillous space is created. This space is where maternal blood bathes the fetal chorionic villi and where fetal-maternal and maternal-fetal exchange occurs (1). Although the intervillous space is an area characterized by low pressure, a pressure differential does exist and ensures adequate circulation. The maternal arteriolar pressure exceeds the pressure in the intervillous space, which exceeds the pressure in the maternal veins. The placenta itself is a low-resistance organ, and, accordingly, the pressure differential across the intervillous space is small. Therefore, the vascular resistance of the maternal arteries governs the rate of flow into and across the intervillous space. During uterine contractions, venous pressure increases. This increased venous pressure causes cessation of flow into the intervillous space. However, the villous space becomes somewhat dilated during a contraction, allowing for continued contact with maternal blood and continued gas exchange, although with reduced efficiency.
The placenta has a high rate of oxygen consumption. It serves as the main organ of gas and nutrient exchange for the fetus (2). However, oxygen extracted at the fetal-maternal interface serves not only the fetus, but the placenta as well. This highly metabolic organ uses as much, and possibly more, of the total oxygen and nutrients as the fetus to maintain its own growth and metabolism (3).
Oxygen consumption remains constant over a wide range of changes in oxygen delivery and will decrease only when extraction is maximal and delivery is further reduced (4). A 50% reduction in uterine blood flow is compensated by an increase in umbilical blood flow and an increase in oxygen extraction to maintain oxygen delivery with no change in fetal oxygen consumption (5). This compensatory mechanism remains adequate only with short-term reductions in uterine blood flow. A critical point exists below which oxygen uptake becomes dependent on oxygen delivery (6). Long-term reductions result in decreased consumption secondary to the decrease in delivery. Below this threshold, tissue hypoxia occurs, there is an inability to maintain oxidative metabolism, and fetal acidemia results (7). A chronic decrease in oxygen consumption also will lead to decreases in both fetal growth and fetal activity in an effort to conserve oxygen for cellular homeostasis (8).
Evidence in sheep indicate that low oxygen-diffusing capacity may be the limiting factor in equilibration of maternal and fetal PO2 across the placenta, particularly in the setting of fetal growth restriction (9). At high altitudes, the diffusion capacity for oxygen increases in an effort to compensate for the low maternal PO2 (10). The administration of maternal oxygen has no effect on uterine or umbilical blood flow but does, however, increase the fetal venous PO2. In situations where fetal oxygen consumption is normal, no increase in fetal oxygen consumption occurs (11). In situations in which fetal oxygen consumption is decreased, maternal administration of oxygen will increase fetal oxygen consumption to near-normal range (12).
The placenta carries oxygenated blood to the fetus via the umbilical vein, while deoxygenated blood is carried back to the placenta via the two umbilical arteries. The human fetal umbilical venous PO2 is low compared to postnatal standards—around 30 mm Hg. Despite this low PO2, adequate amounts of oxygen can be delivered to the fetal tissues. This delivery is facilitated by the high fetal cardiac output, relative to its body size, and the affinity of fetal hemoglobin for oxygen (13). This situation highlights the importance of the high affinity that fetal hemoglobin has for oxygen. Fetal hemoglobin's high affinity for oxygen ensures that virtually all of the fetal hemoglobin is maximally saturated, even at the low PO2 of the fetal umbilical venous blood. This affinity can be altered by factors such as acidosis and temperature. An increase in pH or a decrease in temperature causes a shift of the hemoglobin oxygen dissociation curve to the left, indicating a higher oxygen affinity.
The transfer of carbon dioxide across the placenta is limited by the diffusion capacity. The placenta is highly permeable to carbon dioxide, and transfer across the chorionic villi is accomplished faster than the transfer of oxygen. Also favoring the transfer of carbon dioxide is the higher affinity that maternal blood has for carbon dioxide compared to fetal blood. Finally, the mild respiratory alkalosis that is normally present in the pregnant woman results in a lower PCO2, further enhancing the transfer of carbon dioxide from the fetus to the maternal blood. These physiologic changes also can work to alter the fetal acid-base balance. Alterations in maternal PCO2 content can lead to disturbances in the fetal PCO2 content. If maternal PCO2 is abnormally elevated, fetal transfer is hindered and will result in elevations of fetal PCO2 and fetal acidosis.
Glucose is a major energy source for the fetus. The fetus primarily obtains glucose from maternal blood, but this may be supplemented by its own glycogenolysis. Fetal glucose deprivation does not alter the weight-specific glucose utilization by the fetus. Instead, this utilization causes fetal hypoglycemia, which results in an increase in the maternal-fetal glucose gradient, and thus increased glucose transport across the placenta. Glucose transport is limited by the availability of transport proteins in the placenta as well as maternal blood glucose levels (2). This facilitated transport differs from that of oxygen and carbon dioxide, which is dependent solely on simple diffusion. Severe glucose deprivation and the resultant decrease in placental uptake may result in fetal growth abnormalities due to the decrease in available substrate (3). Chronic glucose deprivation will decrease glucose utilization and increase glycogenolysis and gluconeogenesis by the breakdown of fetal protein. This net protein loss results in fetal growth disturbances and ultimately may lead to growth restriction.
Transport of waste includes lactate. With a drop in oxygen supply and a change to anaerobic metabolism, the fetus begins to produce large amounts of lactate. In this situation, the placenta becomes a major source of lactate clearance from the fetal circulation (14). The placenta, in response to decreased glucose supply, will decrease its consumption of glucose and increase its consumption of lactate to account for the glucose deficit (15).
Fetal Monitoring
Electronic fetal monitoring, introduced in the 1960s, has become ubiquitous in labor and delivery units in developed countries. This type of fetal monitoring typically is used at any gestational age at which ex utero survival is possible. It requires very little in preparation or maintenance but does require an experienced interpreter. This technique results in a continuous tracing of the fetal heart rate, coupled with a tracing of uterine activity.
Regulation of the fetal heart rate is governed by a complex interplay of the sympathetic and parasympathetic nervous systems (16). The sympathetic nervous system exerts influence through the release of norepinephrine, which accelerates the heart rate and increases inotropy. The parasympathetic nervous system influences the fetal heart through the vagus nerve. Stimulation of the vagus nerve leads to a decrease in the heart rate. The fetal heart rate variability results from the constant “push-pull” of these two systems. Gestational age has some effect on the fetal heart rate, with a general decrease in the baseline heart rate occurring with advancing gestation. Finally, fetal heart rate tracing reactivity is defined by the presence of fetal heart rate accelerations. These transient increases in baseline fetal heart rate are due to fetal movement. The presence of reactivity is associated with central nervous system maturation and virtually always is present in a normal fetus after 32 weeks gestational age (17). The absence of fetal heart rate variability for periods of more than 1 hour, and especially in the presence of fetal heart rate decelerations, is associated with fetal acidemia (18).
Decelerations occur when the fetal heart rate falls below the baseline heart rate and are classified according to their location in relation to uterine contractions and their appearance. Different types of decelerations are caused by different mechanisms.
Therefore, each type of deceleration has different implications for fetal well-being.
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Figure 101.1. Early decelerations. Early decelerations mirror the contraction and are not associated with fetal compromise. |
· Early decelerations: Early decelerations begin at the onset of uterine contractions and appear to mirror the contraction (Fig. 101.1). They are believed to be caused by pressure on the fetal head. This pressure results in an alteration in cerebral blood flow and stimulation of the vagal center, with a subsequent decrease in the fetal heart rate. Early decelerations generally are not associated with other ominous findings and are not associated with fetal hypoxia, acidosis, or low Apgar scores.
· Variable decelerations: Variable decelerations are caused by intermittent umbilical cord compression. Although they occur most often during uterine contractions, they may occur at variable times in relation to uterine contractions and may occur even in the absence of contractions (Fig. 101.2). The physiologic basis for these decelerations results from either a chemoreceptor or a baroreceptor response. On initial cord occlusion, there is an increase in fetal peripheral resistance caused by the interruption of the low resistance placental circulation. This results in fetal hypertension and stimulation of the baroreceptors. The baroreceptor response activates the vagus nerve, resulting in fetal heart rate deceleration. Along with the rise in pressure, there is a fall in fetal PO2 with umbilical cord compression. This decrease in arterial oxygen content leads to chemoreceptor activation and stimulation of vagal activity. Frequently, “shoulders” can be seen both preceding and following these variable decelerations. These transient increases in fetal heart rate are a result of venous occlusion and a decrease in blood return to the fetal heart. This decreased cardiac output leads to a compensatory rise in heart rate. Mild or isolated variable decelerations are benign. However, repetitive moderate or severe variable decelerations may indicate fetal compromise (Table 101.1).
· Late decelerations: Late decelerations occur late in relation to the uterine contraction. Their onset begins after the contraction begins, and they resolve after the resolution of the contraction (Fig. 101.3). These decelerations occur as a result of decreased uteroplacental oxygen delivery to the fetus. This intermittent hypoxia, which may or may not be associated with fetal acidemia, also results in fetal hypertension, leading to both a chemoreceptor and baroreceptor response. In the presence of fetal acidemia, this response may also be mediated by direct myocardial depression (17). There are many clinical causes of late decelerations, primarily those that result in maternal hypotension or decreased uterine blood flow. Persistence of late decelerations, especially in the absence of fetal variability, is an ominous sign of fetal compromise.
Other fetal heart rate patterns may be seen in the presence of fetal central nervous system dysfunction. Although the normal fetus may have episodes of decreased heart rate variability of 30 to 40 minutes due to sleep, fetuses with central nervous system dysfunction may exhibit persistently diminished variability. Unstable, or wandering, baseline heart rates also may be seen. Sinusoidal patterns also can be seen in the presence of fetal central nervous system dysfunction. These patterns resemble a sine wave, with a frequency of 3 to 5 cycles per minute and an absence of fetal heart rate variability. Severe fetal anemia is another potential cause of a sinusoidal fetal heart rate tracing (17).
Antenatal Testing
In addition to fetal heart rate monitoring during labor, certain situations may indicate periodic assessments of fetal well-being during the antepartum period. Several of these methods of antepartum fetal surveillance require only electronic fetal monitoring, whereas some involve the use of ultrasound. The primary indication for most aspects of fetal surveillance is the need to evaluate a potentially viable fetus where there is a concern for fetal hypoxia or death, as well as to assess the likelihood of stillbirth during the subsequent week. The goal of fetal surveillance is to identify early fetal hypoxia and prevent prolonged or severe hypoxia that results in perinatal asphyxia. Most tests of fetal well-being lack specificity and have a low positive-predictive value but are used because of their high negative-predictive value. They are frequently used in high-risk obstetric patients but are of limited value when the maternal condition is changing rapidly.
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Table 101.1 Classification of Variable Decelerations |
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Nonstress Test
Nonstress testing involves fetal heart rate monitoring for a period of 20 to 40 minutes. The underlying premise for this test relates to the fact that a nonacidotic, neurologically intact fetus will have fetal heart rate accelerations in response to fetal movement. The presence within a 20-minute window of two fetal heart rate accelerations lasting at least 15 seconds, that peak at least 15 beats per minute above the baseline, characterizes a ‘reactive’ nonstress test and is reassuring (Fig. 101.4). The absence of these accelerations requires further testing or delivery, depending on the gestational age. Fetuses at less than 32 weeks gestational age may not have reactive nonstress tests despite the absence of compromise (19). The nonstress test is simple to perform and generally is required on admission for initial evaluation of fetal well-being. A reactive test is highly reassuring, with a false-negative rate of 1.9/1,000 (20).
Contraction Stress Test
Contraction stress testing can be used as a follow-up test to a nonreactive nonstress test or used alone for fetal evaluation. This test requires at least three spontaneous or elicited contractions during a 10-minute window and evaluates the fetal heart response to these contractions. Due to the necessity of uterine contractions, this test is contraindicated in various situations, including significantly preterm gestations and those in whom labor is contraindicated. The underlying premise for this test involves the idea that fetal oxygenation will transiently worsen in the presence of uterine contractions. In the already compromised fetus, this will result in late decelerations. The contraction stress test is interpreted based on the presence or absence of late decelerations. A positive contraction stress test is one in which late decelerations occur with at least 50% of contractions and generally indicates that delivery is warranted. A negative test result with no late decelerations is highly reassuring, with a false-negative rate of only 0.3/1,000 (Fig. 101.5) (20).
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Figure 101.2. Variable decelerations. Variable decelerations occur at various times in relation to the contraction and are a result of transient umbilical cord compression. |
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Figure 101.3. Late decelerations. Late decelerations occur late in relation to the contraction and may be a sign of fetal compromise. |
Biophysical Profile
The biophysical profile consists of a nonstress test and an ultrasound evaluation of several parameters. This test can be performed as a follow-up test to a nonreactive, nonstress test or can be used as a form of surveillance on its own. The biophysical profile attempts to evaluate the fetus in terms of acute and chronic compromise. The nonstress test is one of the parameters used for evaluation. In addition, an ultrasound examination seeks to evaluate the amount of amniotic fluid, fetal tone, gross body movements, and fetal breathing movements (Table 101.2). The final score is derived from these various assessments, and intervention is based on both the score and gestational age. There are no contraindications to its use, and the entire evaluation takes less than an hour to complete. Many factors may alter the results of the biophysical profile, including maternal sedation, drug use, or hypoglycemia. There is a high correlation with low scores and fetal compromise, and the best predictor of perinatal mortality appears to be the absence of fetal tone (21). Unfortunately, none of these parameters is able to predict acute events such as placental abruption or a cord accident. A normal biophysical profile score of 8 or 10 is very reassuring—the false-negative rate is 0.8/1,000 (20).
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Figure 101.4. Reactive nonstress test. This nonstress test is reassuring, indicating fetal well-being. |
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Figure 101.5. Negative contraction stress test. This contraction stress test is negative, indicating good fetal reserve. |
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Table 101.2 Components and Scoring of the Biophysical Profilea |
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Doppler Velocimetry
Doppler assessment can be accomplished with the use of color Doppler during an ultrasound examination. The umbilical artery is the most widely interrogated vessel for fetal surveillance. In normal fetuses, the umbilical artery has a high diastolic velocity due to low placental resistance (Fig. 101.6). In the presence of placental injury or pathology, the umbilical artery resistance may be increased. As this resistance rises, diastolic flow decreases. With high levels of resistance, this diastolic flow may cease, or even more concerning, actually may become reversed (Fig. 101.7). Reversed end diastolic flow in the umbilical artery is associated with significant perinatal morbidity and mortality. Although large-scale studies have not been performed using umbilical artery Doppler as the main method of surveillance, small randomized controlled trials have indicated that it is a highly effective means of monitoring, with a negative-predictive value approaching 100% (22). A recent meta-analysis confirms the utility of Doppler assessment in the setting of growth restriction and notes a reduction in the number of perinatal deaths with the use of this technology (23). Doppler assessment has not been shown to be of value in the general obstetric population as a form of fetal surveillance in the absence of fetal growth restriction (24).
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Figure 101.6. Doppler velocimetry. Normal umbilical artery Doppler waveform. |
Doppler interrogation of the middle cerebral artery also has been shown to be of benefit in certain situations. In the setting of significant fetal anemia, the blood is “thinner” and the cardiac ejection fraction increases. This increase forces an increase in the velocity of blood through the middle cerebral artery. Periodic middle cerebral artery interrogation is replacing the assessment of amniotic fluid for monitoring fetuses at risk of anemia (25). The use of Doppler measurements from the umbilical artery or middle cerebral artery outside of the clinical settings described or the use of measurements from other vessels currently is investigational.
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Figure 101.7. Abnormal Doppler velocimetry. This umbilical artery Doppler waveform shows reversed end diastolic flow, indicating increased placental resistance. |
Adjuncts to Intrapartum Fetal Heart Rate Monitoring
Fetal Scalp Sampling
As mentioned previously, decelerations can occur in the absence of fetal hypoxia or acidemia. In an effort to delineate fetuses with decelerations and acidemia from those with normal pH, fetal scalp sampling may be performed. This is accomplished by taking a blood sample from the fetal scalp. The normal fetal scalp pH is 7.25 to 7.35, with values below 7.20 considered acidotic (17). This direct evaluation of fetal pH has limitations, in that this test can be performed only in the presence of labor with ruptured membranes. Therefore, this technique is not available for evaluating the preterm fetus, or even the term fetus when the membranes are intact, which limits its use to the intrapartum course. However, in the appropriate setting, this test can be an invaluable tool in the assessment of fetal acidosis. This metabolic acidosis can be treated with an adequate supply of oxygen. If the hypoxic insult is reversible, intrauterine resuscitation is preferred to immediate delivery. This can be accomplished with various techniques to improve maternal, and thus fetal, oxygenation, including the administration of supplemental oxygen and maternal position changes.
Many studies have evaluated fetal scalp stimulation and its relation to fetal pH. Fetuses with a fetal heart rate acceleration in response to digital stimulation of the scalp reliably have a pH of greater than 7.20. However, of fetuses without accelerations, 50% have a normal pH, whereas the remaining 50% are noted to be acidotic (26). Because digital stimulation of the fetal scalp can be performed when the membranes are intact, it requires only a cervix that is dilated. Therefore, this more simple evaluation of fetal pH can be used without ruptured membranes, although its use is still confined to evaluation of the fetus during labor.
Fetal Pulse Oximetry
Fetal pulse oximetry, introduced in the 1980s, initially held promise as a method to further assess the fetal oxygen status in the presence of a nonreassuring fetal heart rate tracing (27). As mentioned previously, the presence of late decelerations does not always indicate a state of persistent hypoxia or acidemia. The ability to directly monitor the fetal arterial oxygen saturation was thought to be an advancement in the ability to accurately predict those fetuses in need of more rapid delivery. A large randomized controlled trial was performed to assess the clinical utility of fetal pulse oximetry in the setting of a nonreassuring fetal heart rate tracing. Unfortunately, the results revealed no benefit in terms of overall cesarean delivery rate, with increased cost in the group using pulse oximetry (28). In response to this study, fetal pulse oximetry is not recommended for routine use and should be used only in the setting of a specific research protocol.
ST Segment Analysis
One of the newest advancements in the field of fetal assessment and electronic fetal monitoring is the ability to combine standard fetal heart rate assessment with an automated analysis of the fetal electrocardiogram, ST waveform analysis. Abnormalities in fetal heart rate tracings, as mentioned previously, have a low predictive value for neonatal acidemia. Fetal ST segment analysis is based on the observation that fetal hypoxia results in characteristic changes in the ST segment as well as the T wave on the fetal electrocardiogram. These changes are thought to be caused by anaerobic metabolism resulting from fetal hypoxia (29). A large Swedish trial comparing electronic fetal monitoring alone with electronic fetal monitoring and ST segment analysis showed a reduction in neonates born with metabolic acidosis when using ST segment analysis (30). Although this technology is not currently used in the United States, trials in this country currently are ongoing and should be reported in the very near future. If future trials support this improved sensitivity in the detection of fetuses with acidosis, ST segment analysis will provide more objective data to allow better identification of those fetuses at risk. ST segment analysis is limited by the need to have a fetal scalp electrode in place. Therefore, it is invasive and can be employed only during labor after the membranes have been ruptured.
Hypoxia
Acute Adaptations
To understand fetal oxygenation, it is necessary to first understand the relationship of maternal to fetal oxygen delivery. As we know from the oxygen dissociation curve, at high partial pressures of oxygen, more oxygen can be bound to hemoglobin. As the hemoglobin protein binds each oxygen molecule, its affinity for oxygen is increased. The opposite also is true, in that, as the oxygen is unloaded at the tissue level, the affinity decreases, allowing for easier uncoupling and supply to the tissue. Various other factors, including pH, temperature, and organic phosphates, can alter that binding. An increase in temperature or decrease in pH causes a decrease in hemoglobin's affinity for oxygen, whereas a decrease in temperature or an increase in pH increases the affinity.
Carbon dioxide in the fetal circulation is exchanged for oxygen from the maternal circulation at the placental interface. The partial pressure of oxygen in the fetal circulation is much lower than that in the maternal circulation. It is this gradient that allows for oxygen transport to the fetus. Fetal hemoglobin is structurally different from adult hemoglobin, consisting of alpha and gamma chains rather than alpha and beta chains. Fetal hemoglobin has an increased affinity for oxygen compared to maternal hemoglobin. This difference in oxygen affinity allows for placental uptake of oxygen even at low partial pressures of oxygen, as is typical in the fetal circulation. At this lower partial pressure of oxygen, the maternal hemoglobin readily is able to unload oxygen, while the fetal hemoglobin readily attracts it. Due to these factors and other adaptations, including a high fetal cardiac output, the fetus normally is able to supply an adequate amount of oxygen to its tissues.
Fetal hypoxia results from either a reduction in placental blood flow or a reduction in oxygen delivery. The process begins with hypoxemia, a reduction in the amount of oxygen carried in the blood as a result of decreased PO2. Although there are attempts at compensation, if these compensatory mechanisms fail, tissue hypoxia results. Energy requirements then are met using anaerobic mechanisms. However, when anaerobic metabolism is insufficient for continued energy demand, permanent tissue damage, organ failure, and asphyxia result (31).
Acute hypoxemia may result from several situations. Cord compression, uterine contractions, and maternal hypotension are frequent causes. Several defense mechanisms allow the fetus to adapt to acute hypoxemia. The fetal brain has a proportionally higher rate of oxygen consumption and therefore requires a high rate of oxygen delivery. To maintain adequate oxygenation, even during times of hypoxemia, the brain is perfused preferentially over other organ systems (32). To shunt blood to the brain, vasoconstriction occurs in the gastrointestinal tract, the skin, and other less essential organ systems. This redistribution of cardiac output via selective peripheral vasoconstriction is mediated by carotid artery chemoreceptor activation. What results is both a decrease in blood flow and oxygen delivery to the peripheral tissues. The accompanying vasodilation that occurs in the brain is most pronounced in the fetal brainstem. Consequently, it has been noted that the fetal brainstem is more resistant to hypoxic damage than are other areas of the brain (33). Tissue mediators, most importantly adenosine, mediate this cerebral vasodilation in response to acute hypoxemia. Adenosine is felt to be neuroprotective in the presence of hypoxemia by controlling oxygen consumption in the brain (34). Certainly, other mediators also influence the vasodilatory effect in the fetal brain; there are suggestions regarding the roles of nitric oxide and opioids. To what degree these other mediators affect the cerebral response to hypoxemia still is under investigation (35).
Along with circulatory centralization mediated by chemoreceptors, metabolic centralization also occurs. Metabolic centralization refers to the fetus's ability to reduce oxygen consumption in the setting of hypoxemia. This process allows the fetus to decrease oxygen delivery to peripheral tissues and allows for increased oxygen delivery to more vital organs. Therefore, when oxygen is in short supply, oxygen delivery still can be maintained to organs such as the brain, heart, and adrenals for continued oxidative metabolism (4). These changes in fetal metabolism contribute to compensatory adaptations to acute hypoxemia. A decrease in oxygen delivery can be compensated for a time. However, once oxygen delivery falls below a critical level, oxygen consumption also falls. Anaerobic metabolism of glycogen allows for maintenance of organ functions in the presence of continued hypoxemia. This anaerobic metabolism, however, leads to the production of lactate and a resulting metabolic acidosis. Lactate accumulates in the fetal tissue and leads to metabolic acidemia. Thus, assessment of fetal pH gives an indirect measure of fetal oxygenation.
Hypoxemia results in decreases in fetal breathing movements, rapid eye movements, general muscle tone and activity, and baseline heart rate (36). These changes minimize the fetus's consumption of oxygen and allow a greater proportion of the cardiac output to be used for maintaining the oxygen supply to the brain (37). Resumption of these activities will occur after several hours, even in the presence of continued hypoxia, as the fetus begins to adapt to a chronic hypoxic condition (38).
Hypoxia affects the fetal heart with a resulting drop in fetal heart rate and ventricular output. There is an elevation in blood pressure but only a small increase in stroke volume (4). To meet the oxygen requirements of the heart, coronary and myocardial blood flow is increased. If hypoxia progresses to acidemia, direct myocardial depression occurs, possibly related to depletion of cardiac glycogen stores. This myocardial depression, in turn, may cause late decelerations seen on fetal heart rate monitoring.
The fetal kidney also is affected by hypoxia. With increasing hypoxia, renal blood flow is decreased, and renal vascular resistance is increased in keeping with the redistribution of cardiac output to the brain, heart, and adrenal glands described previously (39). Prolonged hypoxia will result in a fall in the glomerular filtration rate and a decrease in urine output. The result will be a decrease in the amniotic fluid volume. Studies in sheep show that during recovery from hypoxia, the glomerular filtration rate and urine production actually will increase over control values (40).
Chronic Adaptations
Much of our understanding of the fetal response to chronic oxygen deprivation is a result of animal studies. Prolonged periods of umbilical cord occlusion and reductions in uterine blood flow result in chronic hypoxia for the fetus. The response to chronic hypoxia is different from the response to an acute hypoxic event. In an effort to continue to supply adequate amounts of oxygen to the peripheral tissues, plasma hemoglobin concentrations rise. Vascular endothelial growth factor and erythropoietin are part of the endocrine response to chronic hypoxia. These factors have neuroprotective effects through both direct action on the neuron and stimulation of angiogenesis and thus act to reduce neuronal injury in the presence of hypoxia (41). Blood flow, previously centralized to the brain, begins to normalize. Although cardiac output is depressed by continued hypoxia, the cerebral vasodilation and cerebral blood flow is maintained. Some studies have shown that under chronic hypoxic conditions, an increase in the synthesis of adrenomedullin, a vasodilator in the fetal cerebral cortex, may allow adequate oxygen delivery, even under low oxygen conditions (42). The increased cerebral blood flow to the brainstem that occurred acutely continues as the hypoxia becomes chronic.
Vascular resistance is increased in the setting of chronic hypoxia. This elevated resistance continues to allow the shunting of blood and oxygen preferentially to the brain. Maintenance of brain growth continues to be a priority even in the presence of continued hypoxia. Other organ systems grow at a disproportionately slower rate, and overall fetal weight is slowed. Meanwhile, the increased resistance in vascular beds, such as the gastrointestinal tract, may set the stage for neonatal complications such as necrotizing enterocolitis. This increase in vascular resistance is evident in Doppler studies of the umbilical arteries.
Some evidence points to changes in the venous circulation with chronic hypoxia. It has been noted that ductus venosus flow is increased in the fetus during periods of hypoxia (43). The increase in ductus venosus flow results in a decrease in flow through the liver, and the fall in hepatic perfusion may impair the liver's ability to synthesize and store glycogen. This situation leads to a decreased substrate available for continued fetal growth. The increase in ductus venosus flow is maintained, even in the presence of severe growth restriction. Some studies have associated a finding of decreased or absent flow in the ductus venosus during atrial systole as a late finding in the fetus's response to hypoxia. This finding has been further implicated in poor perinatal outcome (44).
Deep inspiratory efforts and fetal gasping occur with severe hypoxia/asphyxia. Although this inspiratory-like reflex is not effective in the fetus, it has been reported as a preterminal event in animal studies. With normalization of fetal oxygenation, even after prolonged periods of hypoxia, fetal breathing movements and fetal movements can return to normal. These events may occur, however, even in the presence of significant brain damage, including reduced myelination and periventricular necrosis (45). Therefore, fetal heart rate monitoring is limited in its ability to predict poor outcome in cases when significant hypoxic episodes occurred prior to the monitoring period. Prolonged periods of hypoxia have an effect on fetal heart rate—similar to the effect on fetal movements. Initially, bradycardia may be noted, followed by a reflex tachycardia. However, in the absence of acidemia, fetal heart rate will return to normal baseline after 12 to 16 hours (46).
Summary
The presence of the fetus and the physiologic changes that occur during pregnancy significantly complicate the care of the pregnant woman. The ability to accurately evaluate the status of the fetus is limited by current technology. Although most tests of fetal surveillance can reassure the clinician that the fetus is in good condition, the positive-predictive value of nonreassuring results is low, and testing may lead to intervention when the fetus actually is not in jeopardy. As newer methods of evaluating the fetal response to stress and hypoxia are developed, our ability to accurately identify fetuses truly at risk will improve. Despite the limitations of the current methods, frequent monitoring of fetal status in the pregnant critically ill patient is used to guide treatment. Consultation either with maternal-fetal medicine specialists or general obstetrician-gynecologists will improve the ongoing care of pregnant patients, as these physicians are more familiar with the physiologic changes that occur in pregnancy and the methods used to evaluate the fetus.
Pearls
· Determination of fetal viability is the first priority in the initial assessment of a pregnant patient.
· Fetal hemoglobin's high affinity for oxygen ensures maximal saturation of fetal hemoglobin.
· The primary indication for most aspects of fetal surveillance is the need to evaluate a potentially viable fetus when there is a concern for fetal hypoxia or death.
· The goal of fetal surveillance is to identify early fetal hypoxia and prevent prolonged or severe hypoxia resulting in perinatal asphyxia.
· Persistence of late decelerations, especially in the absence of fetal heart rate variability, is an ominous sign of fetal compromise.
· Antenatal fetal assessment includes the use of a nonstress test, biophysical profiles, and Doppler velocimetry.
· To maintain adequate oxygenation, even during times of hypoxemia, the brain is perfused preferentially over other organ systems.
· When oxygen is in short supply, oxygen delivery still can be maintained to organs such as the brain, heart, and adrenals for continued oxidative metabolism.
· Although the negative-predictive values are high, the positive-predictive values of all tests of fetal well-being are low.
· Consultation either with maternal-fetal medicine specialists or general obstetrician-gynecologists is recommended.
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